Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization

Abstract

Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide–specific and total plasmablasts in blood. Moreover, increased responses of blood mucosa-associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

“…Th17 CD4+ T cells were shown to mediate the clearance of pneumococcal colonization in mice [28,29]. Recent work using an experimental colonization challenge in humans failed to find an association between Th17 or any CD4+ T memory cells and the control of colonization [30,31]. Rather, individuals with a higher concentration of CXCL10 prior to challenge were shown to have higher bacterial loads [30].…”

“…Furthermore, B cells were shown to be depleted in the nasal mucosa following establishment of carriage due to recirculation of activated B cells. CD8+ mucosa-associated invariant T (MAIT) cell responses were associated with protection against pneumococcal carriage [31].…”

Human immunology and immunotherapy: main achievements and challenges

“…For allergies, EWAS has mainly been performed on nasal mucosal cells and whole blood (although the result was later normalized by the number of circulating eosinophils). Nasal mucosal cells comprise CD8 + T cells, CD4 + T cells, myeloid cells, innate lymphoid cells, B cells, double-negative T cells, granulocytes, CD117 + cells, and plasma cell populations 165 . In all of these studies, 36 CpG-associated regions were identified, from which the SMAD3 gene, coding for an important regulator of T-cell differentiation, was replicated in three independent cohorts 166 .…”

Progress and applications of mass cytometry in sketching immune landscapes

“…Recent progress and applications illuminate the salient features and the prospects of CyTOF in sketching the immune landscape. In essence, CyTOF can picture both innate 77,137,165,166 and adaptive 123,167 immune landscapes, which includes numerous phenotypically and functionally heterogeneous cell subsets of lymphoid and myeloid lineages that are involved in adequate surveillance and pathogens killing. Panoramic views of systemic immunity involving circulation and infiltration can also be obtained.…”